Melanoma has been on the rise for decades. It is presently the seventh most common cancer in the United States. It is currently estimated that by the year 2000 the lifetime risk of developing skin melanoma in Americans will be 1 in 75. The annual incidence of human melanoma worldwide is increasing at the rate of approximately 5% per year (16, 17). Due to its propensity to metastasize early, coupled to the common feature of late recurrence, relapses from melanoma represent an important and often life threatening clinical condition. The cancer starts in the skin, but frequently spreads. It can spread locally or throughout the body. Tissues with melanomas can include lymph glands, liver, bones, brain, lung, adrenal glands, the spinal cord, and vertebrae. Although, once melanoma has spread beyond the original skin site it is currently considered incurable, there are treatment modalities that can prolong an individual's survival.
Metastatic diseases of unknown origin are fairly common. Melanoma resides among the tumor types more commonly associated with metastases lacking an obvious primary tumor site (18-22). It has proven difficult to determine if such metastatic tissue is melanoma. One of the problems is that when a melanoma is not found on the skin, its diagnosis is problematic. Currently, there are two markers typically used to diagnose melanoma. These markers have problems because the first marker, S100, while sensitive and present in about 80% of melanoma, is also widely present in non-melanoma tumors [Kahn, H. J., et al., American J. of Clin. Pathol. 79:341-471 (1983). Thus, it also stains a significant number of nonmelanoma malignancies. The second marker, HMB-45, while very specific for melanoma, only detects about 50% of melanomas [Applied Immunolohistochemisty 4:73-95 (1996)]. Other estimate for HMB-45 have ranged as low as 5% and it has been suggested that it stains variably in a technique-dependent fashion (23, 27, 29, 30, 32-35). Thus, there is a need for other markers that will specifically detect melanoma.
Determining the origin of a metastatic tissue arising from a melanoma is extremely difficult. For example, a skin melanoma can be removed, yet come back years later at a different site. Conversely, the fact that someone had a melanoma removed 20 years ago, does not mean that a metastatic disease of unknown origin would necessarily be a melanoma because that individual could have developed a different cancer. Thus, the ability to determine the origin of a metastatic disease is very important because it can affect the diagnosis and/or the type of treatment regime prescribed. It would be extremely important if a better and more accurate means for diagnosing melanoma was available. It would also be important having a better means to determine prognosis.
Another problem with melanomas involves the treatment thereof. It is important to be able to selectively treat the malignant tissue and not the surrounding normal tissues. Side effects are frequently experienced from current treatments because some normal tissue is also harmed. Means for improving the selectivity are desired.